Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus

By Ben Hu, Lei-Ping Zeng, Xinglou Yang, Xingyi Ge, Wei Zhang, Bei Li, Jiazheng Xie, Xurui Shen, Yun-zhi Zhang, Ning Wang and 7 more. PLoS Pathogens, 2017

947 citations recorded by the source corpus.

A large number of SARS-related coronaviruses (SARSr-CoV) have been detected in horseshoe bats since 2005 in different areas of China. However, these bat SARSr-CoVs show sequence differences from SARS coronavirus (SARS-CoV) in different genes (S, ORF8, ORF3, etc) and are considered unlikely to represent the direct progenitor of SARS-CoV. Herein, we report the findings of our 5-year surveillance of SARSr-CoVs in a cave inhabited by multiple species of horseshoe bats in Yunnan Province, China. The full-length genomes of 11 newly discovered SARSr-CoV strains, together with our previous findings, reveals that the SARSr-CoVs circulating in this single location are highly diverse in the S gene, ORF3 and ORF8. Importantly, strains with high genetic similarity to SARS-CoV in the hypervariable N-terminal domain (NTD) and receptor-binding domain (RBD) of the S1 gene, the ORF3 and ORF8 region, respectively, were all discovered in this cave. In addition, we report the first discovery of bat SARSr-CoVs highly similar to human SARS-CoV in ORF3b and in the split ORF8a and 8b. Moreover, SARSr-CoV strains from this cave were more closely related to SARS-CoV in the non-structural protein genes ORF1a and 1b compared with those detected elsewhere. Recombination analysis shows evidence of frequent recombination events within the S gene and around the ORF8 between these SARSr-CoVs. We hypothesize that the direct progenitor of SARS-CoV may have originated after sequential recombination events between the precursors of these SARSr-CoVs. Cell entry studies demonstrated that three newly identified SARSr-CoVs with different S protein sequences are all able to use human ACE2 as the receptor, further exhibiting the close relationship between strains in this cave and SARS-CoV. This work provides new insights into the origin and evolution of SARS-CoV and highlights the necessity of preparedness for future emergence of SARS-like diseases.

Subfields: Animal Science and Zoology, Genetics, Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/1a2c3991a18171055b98f12c29a2c1f5d5fef1bd

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Citations in the corpus

The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2 (2020, result): “These relationships stand in contrast to the shallow branching of the most populous lineage of this species, which includes all the human SARS-CoV isolates collected during the 2002-2003 outbreak and the closely related bat viruses of Asian origin identified in the search for the potential zoonotic ”
Origin and evolution of pathogenic coronaviruses (2018, positive): “The tree is based on published trees 20,138 and reconstructed using sequences of the complete RNA dependent RNA polymerase coding region (maximum likelihood method under the GTR + I + Γ model of nucleotide substitution as implemented in PhyML , version 3.1 (rEF.”
The COVID-19 Pandemic: A Comprehensive Review of Taxonomy, Genetics, Epidemiology, Diagnosis, Treatment, and Control (2020, background): “Therefore, SARS-CoV likely emerged through recombination of bat SARS-like CoVs before infecting civets, from which the recombinant virus spread to humans, causing the SARS epidemic [5,26].”
Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding (2020, positive): “There is a dizzying diversity of RBD genotypes and phenotypes among sarbecoviruses within bat reservoirs (Boni et al.; Demogines et al., 2012; Frank et al., 2020; Hu et al., 2017; Latinne et al., 2020; Letko et al., 2020; MacLean et al., 2020).”
Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding (2020, positive): “There is a dizzying diversity of RBD genotypes and phenotypes among sarbecoviruses within bat reservoirs (Boni et al., 2020; Demogines et al., 2012; Frank et al., 2020; Hu et al., 2017; Latinne et al., 2020; Letko et al., 2020; MacLean et al., 2020).”
Molecular Diagnosis of a Novel Coronavirus (2019-nCoV) Causing an Outbreak of Pneumonia (2020, background): “It is now generally believed that SARS coronavirus is a recombinant virus between several bat SARS-like beta-coronaviruses (9).”
Effective treatment of severe COVID-19 patients with tocilizumab (2020, background): “The elderly and patients with low immune function have a higher susceptibility and mortality (1).”